[Severe psychosis in an African woman due to the antiretroviral agent efavirenz]. / Ernstige psychose bij een afrikaanse vrouw door het antiretrovirale middel efavirenz.

A 34-year-old woman originally from Ghana was given efavirenz as antiretroviral therapy. One week later she was found to be in a psychotic state with paranoid hallucinations and anxiety; she then stabbed a nurse. The literature indicates that female patients of African origin appear to be more susceptible to the side effects of efavirenz due to genetically reduced clearance and therefore higher serum levels.

The effect of single twitch and train-of-four stimulation on twitch forces during stable neuromuscular block.

OBJECTIVE: We investigated whether the response to a single twitch (ST) stimulus or the first response (T1) to a train-of-four (TOF; 4 stimuli at 2 Hz) stimulus following a stimulus interval of 10 s (i.e., the time between two consecutive ST or TOF stimuli) is influenced by the preceding stimulus in the presence of a stable 50% neuromuscular block. In addition, we determined whether ST and TOF stimulation yield different results under these circumstances. METHODS: Twitch forces were measured in both tibialis anterior muscles of six cats. In the presence of a stable 50% neuromuscular block the stimulation pattern (ST or TOF) or stimulus interval (3.3, 10 or 30 s) was varied every 30 min. A linear mixed model was used for statistical analysis. RESULTS: ST forces with a stimulus interval of 3.3 s were 10.3% (95% CI: 7.3-13.3%) smaller than those with a stimulus interval of 10 s. For T1 forces this effect was 15.2% (95% CI: 12-18.4%). There was no significant difference between twitch forces with stimulus intervals of 30 and 10 s. For a stimulus interval of 3.3 s the ST forces exceeded the T1 forces by 7.6% (95% CI: 4.4-10.8%); no significant differences were found between the ST and T1 forces for stimulus intervals of 10 and 30 s. CONCLUSIONS: The ST or T1 force during stimulation with a stimulus interval of 10 s or more during a stable 50% neuromuscular block in the tibialis anterior muscle of the cat is not affected by the preceding stimulus. In addition, ST and T1 forces do not differ when employing a stimulus interval of 10 s or more under these circumstances. Our results thus indicate that the known differences between ST and T1 forces after a bolus injection of a muscle relaxant can not be explained by differences in acetylcholine release when the stimulus interval exceeds 10 s.

[Dyspnea caused by bullae in a muscular dystrophy patient on chronic intermittent ventilatory support]. / Dyspneu door bullae bij een chronisch intermitterend beademde patiënt met spierdystrofie.

A 65-year-old patient, ex-smoker, with facioscapulohumeral muscular dystrophy (FSHD) had been on home non invasive ventilatory support for three years when he experienced gradual increase of dyspnoea. The chest radiograph showed large bullae occupying most of the right hemithorax, with compression of lung tissue, mediastinal shift, and compression of the left lower lobe. Bullectomy resulted in rapid clinical and radiographic improvement. This is the first report of beneficial effects of emergency bullectomy in FSHD. Bullectomy has proved most successful in patients with localized bullae and compression of surrounding lung tissue. Patients with respiratory infections and bronchiectasis benefit less.

Increase in twitch force of the adductor pollicis muscle with stabilized preload at constant thumb abduction before and after administration of muscle relaxant.

OBJECTIVE: To determine whether the twitch force of the adductor pollicis remains stable when 0.1 Hz single twitch stimulation is started after stabilization of the thumb preload at a constant degree of thumb abduction; also to study any possible increase in twitch force before the onset of and after the recovery from neuromuscular block. METHODS: Measurements were performed in thirty patients under general anaesthesia. Twitch forces were first allowed to stabilize after allowing the preload to drift to its resting tension at a constant degree of thumb abduction. Three groups of ten patients then each received either vecuronium (2, 4, 8, 16 and 32 microg/kg(-1), successively at intervals of 2 min), d-tubocurarine (5, 10, 20, 40 and 80 microg/kg(-1), successively at intervals of 2 min), or suxamethonium (0.025, 0.05, 0.1, 0.2 and 0.4 mg/kg(-1), successively at intervals of 2 min). Measurements were continued until twitch forces had recovered from neuromuscular block and were stable. RESULTS: Twitch forces stabilized at 114% (sd = 8.9) of the initial value after 10.9 (6.1) min of stimulation. Increase in twitch force before the onset of neuromuscular block was seen in two patients receiving vecuronium and in two patients receiving d-tubocurarine. Increase in twitch force after recovery from neuromuscular block was seen in all patients receiving suxamethonium. CONCLUSIONS: Twitch forces may increase when stimulation is started after stabilization of thumb preload at a constant degree of thumb abduction. In some patients twitch forces may increase before the onset of neuromuscular block with vecuronium or d-tubocurarine; twitch forces increase after recovery from suxamethonium.

The effect of maintaining a constant preload or a constant degree of thumb abduction in the isometric twitch force of the thumb.

OBJECTIVE: To investigate the effects of maintaining a constant preload and of maintaining a constant degree of thumb abduction on the isometric twitch force during mechanomyography of the thumb, we monitored neuromuscular function in patients anaesthetized without the use of a neuromuscular blocking agent. In addition, we studied the relationship between the degree of thumb abduction, twitch force and preload. METHODS: Fourteen patients were divided randomly into two groups, determining the sequence of the experiments in respect of correcting the preload and maintaining a constant degree of abduction after allowing the twitch forces to stabilize. Both experiments lasted 15 minutes. In both groups the relationship between the degree of thumb abduction, twitch force and preload was studied. RESULTS: We found a progressive increase in twitch force both with (6.6%; CI: 3.7-9.3%; p < 0.001) and without (1.9%; CI: 0.4-3.5%; p = 0.020) continuous correction of the thumb preload. A significant greater increase in twitch force was seen when the preload had been corrected than when it was not (4.7%; CI: 0.8-8.7%; p = 0.023). In addition, both twitch force and preload appeared to depend on the degree of thumb abduction both before and at the time of measurement. CONCLUSIONS: Changes in length of the contracting muscle fibres and creep phenomena in the connective tissue of the muscles, both leading to changes in the sarcomere length of the muscle fibres, may explain the observations in this study. In general, a stabilized preload at a constant degree of abduction seems to be required in order to obtain a stable twitch force.

Stabilization and stability of twitch force during mechanomyography of the adductor pollicis muscle.

OBJECTIVE: In order to study the stabilization time, the increase in twitch force during stabilization and the maintenance of stability during mechanomyography of the adductor pollicis muscle, neuromuscular function was monitored in 20 patients anaesthetized without the use of a neuromuscular blocking agent. The effect of the type of stimulation (single twitch [ST; 0.1 Hz], or train-of-four [TOF; 4 stimuli at 2 Hz, repeated every 12 s]) on these variables was studied. When applying TOF stimulation, the variables were also investigated for the TOF percentage [quotient of fourth and first twitch of a TOF stimulus x 100%]. METHODS: Two groups of ten patients were monitored with either ST or TOF stimulation. Measurements continued for at least 45 minutes. Multiple linear regression analysis was applied to examine the effect of stimulation on the stabilization time and the increase in twitch force. RESULTS: According to our criteria for stability, we found that the stabilization time did not differ for ST (13.7 [10.2] min; mean [sd]) and TOF stimulation (18.1 [9.6] min) (p > 0.10). Stabilized twitch forces were larger during TOF than during ST stimulation (134% [19] and 113% [11]; p = 0.01). In both groups of stimulation, six patients showed an interruption of stability. The TOF percentage was stable throughout the measurement period in all patients. CONCLUSIONS: Stabilization of twitch force takes too long for many studies of neuromuscular function in the clinical research setting. Therefore, we do not recommend its routine use when performing mechanomyography of the adductor pollicis muscle.

Clinical pharmacology of rocuronium (Org 9426): study of the time course of action, dose requirement, reversibility, and pharmacokinetics.

STUDY OBJECTIVE: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol, halothane, or isoflurane). DESIGN: Prospective, randomized study. SETTING: Operating suite at a university hospital. PATIENTS: 36 ASA physical status I-III patients aged 18 to 65 years who were scheduled for elective surgery. INTERVENTIONS: The time course of action of an intubation dose of rocuronium 600 micrograms/kg was investigated in 36 patients. In 18 of these patients, the maintenance dose requirement of rocuronium and reversibility by neostigmine were evaluated. In the remaining 18 patients, the pharmacokinetics of rocuronium after the intubating dose were studied. Neuromuscular transmission was monitored by mechanomyography. Venous blood samples and urine were analyzed by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: With the exception of a longer clinical duration of rocuronium-induced neuromuscular block in the isoflurane group compared with the propofol group (p = 0.03), time course of action variables were similar in the 3 groups. In patients receiving maintenance doses of rocuronium, the dose requirement until reversal was 636 +/- 191 micrograms/kg/hr, 496 +/- 107 micrograms/kg/hr, and 384 +/- 127 micrograms/kg/hr for the propofol, halothane, and isoflurane groups, respectively (p = 0.02 for the isoflurane group vs. the propofol group). With respect to the reversal of a rocuronium-induced neuromuscular block, there were no differences in the percentage recovery or rate of recovery among the 3 groups. Pharmacokinetic analysis showed no significant differences for rocuronium during the 3 anesthetic techniques. CONCLUSION: Isoflurane potentiates the rocuronium-induced neuromuscular block, resulting in a longer clinical duration and lower maintenance dose requirement. This difference is not explained by differences in pharmacokinetics but is probably due to increased sensitivity of the neuromuscular junction to rocuronium during isoflurane anesthesia.

The 'methadone by bus' project in Amsterdam.

One of the methadone programmes of the Amsterdam Municipal Health Service is the 'methadone by bus' project. Two mobile clinics cruise the city, stopping at six different locations daily. The liquid methadone is consumed on the spot and clean needles and condoms are available. This project is based on the principles of 'harm-reduction', i.e. if it is not (yet) possible to 'cure' a hard drug user, one should at least try to minimize the harm they cause to themselves and their environment. As soon as a client refrains from the use of illegal drugs, the client can 'graduate' to other methadone programmes with a higher threshold. To prevent double prescription, all Amsterdam methadone programmes participate in the central methadone registration. The Amsterdam Municipal Health Service has contact with over 50% of the drug users. The estimated number of hard drug users has remained stable over the last 5 years, whilst the average age of drug users has increased to 32 years. In the future, increasing the average dosage and the provision of injectable drug users will be discussed to assess their role in further harm reduction.

The impact of the needle and syringe-exchange programme in Amsterdam on injecting risk behaviour.

We interviewed a group of 145 injecting drug users (IDUs) in Amsterdam about their drug use, participation in a needle-exchange programme and needle sharing. Approximately 1 year later 60 IDUs were followed up. IDUs who exchange regularly ('exchangers') are older, inject longer and are more often in contact with methadone programmes. Exchanging is associated neither with an increase in injecting nor with lending needles to other IDUs. The risk level of injecting of the exchangers is much lower than that of the non-exchangers. From this it can be concluded that a needle exchange is an effective prevention programme against the spread of HIV infection. However, efforts have to be made to reach the group of younger short-term injectors and those IDUs who are not in contact with methadone-maintenance programmes. Since there are indications that regular injectors in particular exchange, and since young male injectors are more at risk of borrowing independent of exchanging, it is argued that an exchange programme should be complemented with other prevention approaches, i.e. intensive counselling and the spread of leaflets with information on cleaning used needles with bleach.

Amsterdam's drug policy and its implications for controlling needle sharing.

In summary, it can be stated that Amsterdam has a wide variety of helping modalities. Approximately 70 percent of the city's 7,000 drug addicts are in contact with this helping system. In The Netherlands, no evidence could be found to support the fear that low-threshold methadone programs keep addicts away from drug-free treatment. Figure 1 shows that the number of addicts entering drug-free treatment doubled in the period 1981-85 (most popular has been the drug-free aftercare). This is even more striking since the estimated number of addicts did not increase in that same period. So, instead of keeping addicts away from treatment, low-threshold programs and outreach activities may have been effective tools in motivating addicts to enter drug-free treatment. Figure 2 shows the rise of the mean age of drug addicts, while figure 3 indicates that the percentage of addicts under 22 years decreases (14.4 percent in 1981 and 5.1 percent in 1986). Since the total number of addicts is quite stable, this may suggest that heroin is becoming less attractive to young people.